10-113590836-GCG-ACA

Variant names:

• chr10-113590836-GCG-ACA
• NM_198060.4:c.4696_4698delCGCinsTGT
• NRAP p.Arg1566Cys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_198060.4(NRAP):​c.4696_4698delCGCinsTGT​(p.Arg1566Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.00000798 in 2 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: GnomAD MNV: 𝑓 0.0000080 Genomes: not found (cov: 32)
• Consequence: NRAP NM_198060.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• Publications: 0 publications found

Genes affected

NRAP (HGNC:7988): (nebulin related anchoring protein) Predicted to enable actin filament binding activity and muscle alpha-actinin binding activity. Predicted to be involved in cardiac muscle thin filament assembly. Predicted to be located in fascia adherens; muscle tendon junction; and myofibril. Predicted to be active in Z disc. [provided by Alliance of Genome Resources, Apr 2022]

NRAP Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198060.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRAP	NM_198060.4	MANE Select	c.4696_4698delCGCinsTGT	p.Arg1566Cys	missense	N/A	NP_932326.2
	NRAP	NM_001261463.2		c.4696_4698delCGCinsTGT	p.Arg1566Cys	missense	N/A	NP_001248392.1	A0A0A0MRM2
	NRAP	NM_006175.5		c.4591_4593delCGCinsTGT	p.Arg1531Cys	missense	N/A	NP_006166.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRAP	ENST00000359988.4	TSL:1 MANE Select	c.4696_4698delCGCinsTGT	p.Arg1566Cys	missense	N/A	ENSP00000353078.3	Q86VF7-1
	NRAP	ENST00000369358.8	TSL:1	c.4696_4698delCGCinsTGT	p.Arg1566Cys	missense	N/A	ENSP00000358365.4	A0A0A0MRM2
	NRAP	ENST00000360478.7	TSL:1	c.4591_4593delCGCinsTGT	p.Arg1531Cys	missense	N/A	ENSP00000353666.3	Q86VF7-4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

GnomAD MNV AF: 0.00000798 AC: 2 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-115350595;